[Bone marrow transplantation with T-cell depletion and hyperfractionated whole-body irradiation. The radiobiological and clinical correlations].

Total body irradiation (TBI) and cyclophosphamide (Cy) is the conventional conditioning regimen for the patients who are to receive bone marrow transplantation (BMT). It is one of the most effective treatments for acute and chronic leukemias. In this paper we discuss the clinical and radiobiological features relative to TBI methods and to the kind of BMT. Graft-versus-host disease (GvHD) incidence is decreased by the depletion of T-lymphocytes from donor's bone marrow which causes high rates of rejection and relapses. Thus, more aggressive conditioning regimens are necessary than unmanipulated BMT. The results are also examined of different experimental and clinical trials on the immunohematological features of T-depleted BMT and the radiobiological behavior of normal and pathological target tissues due to different methods of TBI. We report the experience of the Perugia Bone Marrow Transplantation Unit and Radiation Oncology Service. We treated 54 patients suffering from acute leukemia (AL) and 34 cases with chronic myeloid leukemia (CML) with T-depleted allogeneic HLA-identical BMT. Three different conditioning regimens were employed in an effort to enhance cytoreduction and immunosuppression without significantly increasing extramedullary toxicity. TBI was administered according to a hyperfractionated scheme of 3 fractions a day for 4 days. The third conditioning regimen, including also thiothepa (TT), gave the best results in terms of stable uptake and leukemic cells eradication. Disease-free survival (DFS) is 55.5% in the patients with AL at a median follow-up of 40 months; in the patients with CML who were not treated with TT, DFS is 10% at a median follow-up of 60 months, while it is 66.6% at a median follow-up of 12 for the group of patients who received also TT. The conditioning regimen with hyperfractionated TBI, Cy and TT was effective and well tolerated; 12.5% of patients developed interstitial pneumonia.